, Volume 235, Issue 1, pp 245–255 | Cite as

Long-term metabolic effects of aripiprazole, ziprasidone and quetiapine: a pragmatic clinical trial in drug-naïve patients with a first-episode of non-affective psychosis

  • Javier Vázquez-BourgonEmail author
  • Rocío Pérez-Iglesias
  • Víctor Ortiz-García de la Foz
  • Paula Suárez Pinilla
  • Álvaro Díaz Martínez
  • Benedicto Crespo-Facorro
Original Investigation



The use of second-generation antipsychotics (SGA) has been associated with metabolic changes. However, there are differences in the metabolic profile between SGAs. We have previously observed that ziprasidone had a more benign early metabolic profile compared to aripiprazole and quetiapine. However, a long-term follow-up is preferred to detect clinically relevant impairment in metabolic parameters. We aimed to compare the effect of aripiprazole, ziprasidone, and quetiapine on metabolic measures in first-episode non-affective psychosis patients after 1 year of treatment.

Material and methods

One hundred and sixty-five drug-naïve patients, suffering from a first episode of non-affective psychosis, were randomly assigned to receive quetiapine, ziprasidone, or aripiprazole. Weight and glycemic/lipid parameters were recorded at baseline and after 1 year of treatment.


After 1 year of antipsychotic treatment, we found significant increments in weight, BMI, total cholesterol, LDL-cholesterol, triglycerides, and the triglyceride/HDL index in the sample as a whole. These changes produced a significant rise in the percentage of patients with obesity, hypercholesterolemia, and hypertriglyceridemia. However, when comparing the differential effect of each antipsychotic medication, we found no significant differences in any of the metabolic parameters between antipsychotics groups after 1 year of treatment.


We concluded that the antipsychotics studied present similar metabolic profiles. However, the primary exposure to SGAs during the first year of psychosis was associated with significant increases in weight and metabolic parameters, leading to increments in obesity, hypertriglyceridemia, and hypercholesterolemia.


Glucose Cholesterol Triglycerides Weight gain Medication-naïve Second-generation antipsychotic 



This study was conducted as part of a clinical trial “Comparative Study of Aripiprazole, Quetiapine and Ziprasidone in the Treatment of First Episode Non-affective Psychosis (AZQ2005).” Identifier: NCT02305823.

The authors wish to thank all “Programa Asistencial de las Fases Iniciales de Psicosis” (PAFIP) research team and all patients and family members who participated in the study.

Author contributions

BC-F designed the study and wrote the protocol. PSP evaluated the patients and collected the study variables. VO-G built and maintained the database and helped with the statistical analyses. RP-I and JV-B managed the literature searches. JV-B undertook the statistical analysis and wrote the first draft of the manuscript. ADM, RP-I, and BC-F contributed to the interpretation of the data and revised the manuscript critically. All authors contributed to and have approved the final manuscript.

Funding information

The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Instituto de Salud Carlos III PI020499, PI050427, PI060507; Plan Nacional de Drogas Research Grant 2005-Orden sco/3246/2004; SENY Fundació Research Grant CI 2005–0308007; and Fundación Marqués de Valdecilla API07/011. Unrestricted educational and research grants from AstraZeneca, Pfizer, Bristol-Myers Squibb, and Johnson & Johnson provided support for PAFIP activities. No pharmaceutical industry or institutional sponsors participated in the study concept and design, data collection, analysis and interpretation of the results, and drafting the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

213_2017_4763_MOESM1_ESM.docx (12 kb)
ESM 1 (DOCX 11 kb)
213_2017_4763_MOESM2_ESM.doc (62 kb)
ESM 2 (DOC 62 kb)
213_2017_4763_MOESM3_ESM.docx (18 kb)
ESM 3 (DOCX 17 kb)
213_2017_4763_MOESM4_ESM.doc (86 kb)
ESM 4 (DOC 86 kb)


  1. Alptekin K, Hafez J, Brook S et al (2009) Efficacy and tolerability of switching to ziprasidone from olanzapine, risperidone or haloperidol: an international, multicenter study. Int Clin Psychopharmacol 24:229–238CrossRefPubMedGoogle Scholar
  2. Andreasen N (1983) Scale for the assessment of negative symptoms (SANS). University of Iowa, Iowa CityGoogle Scholar
  3. Andreasen N (1984) Scale for the assessment of positive symptoms (SAPS). University of Iowa, Iowa CityGoogle Scholar
  4. Bonfioli E, Berti L, Goss C et al (2012) Health promotion lifestyle interventions for weight management in psychosis: a systematic review and meta-analysis of randomized controlled trials. BMC Psychiatry 12:78CrossRefPubMedPubMedCentralGoogle Scholar
  5. Breier A, Berg PH, Thakore JH et al (2005) Olanzapine versus ziprasidone: results of a 28-week double-blind study in patients with schizophrenia. Am J Psychiatr 162:1879–1887CrossRefPubMedGoogle Scholar
  6. Carvalho AF, Sharma MS, Brunoni AR et al (2016) The safety, tolerability and risks associated with the use of newer generation antidepressant drugs: a critical review of the literature. Psychother. Psychosomatics 85(5):270–288Google Scholar
  7. Chacón F, Mora F, Gervás-Ríos A et al (2011) Efficacy of lifestyle interventions in physical health management of patients with severe mental illness. Ann Gen Psychiatry 10:22CrossRefPubMedPubMedCentralGoogle Scholar
  8. Chue P, Mandel FS, Therrien F (2014) The effect of ziprasidone on metabolic syndrome risk factors in subjects with schizophrenia: a 1 year, open-label, prospective study. Curr Med Res Opin 30(6):997–1005CrossRefPubMedGoogle Scholar
  9. Correll CU, Manu P, Olshanskiy V et al (2009) Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA 302:1765–1773CrossRefPubMedPubMedCentralGoogle Scholar
  10. Correll CU, Robinson DG, Schooler NR et al (2014) Cardiometabolic risk in patients with first-episode schizophrenia spectrum disorders: baseline results from the RAISE-ETP study. JAMA Psychiatry 71(12):1350–1363CrossRefPubMedGoogle Scholar
  11. Crespo-Facorro B, Ortiz-Garcia d l FV, Mata I et al (2013) Aripiprazole, ziprasidone and quetiapine in the treatment of first-episode non-affective psychosis: a 12-week randomized, flexible-dose, open-label trial. Schizophr Res 147:375–382CrossRefPubMedGoogle Scholar
  12. Crespo-Facorro B, de la Foz VO, Mata I et al (2014) Treatment of first-episode non-affective psychosis: a randomized comparison of aripiprazole, quetiapine and ziprasidone over 1 year. Psychopharmacology 231(2):357–366CrossRefPubMedGoogle Scholar
  13. Crespo-Facorro B, Pelayo-Teran JM, Mayoral-van Son J (2016) Current data on and clinical insights into the treatment of first episode nonaffective psychosis: a comprehensive review. Neurol Ther 5(2):105–130. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Daniel DG, Zimbroff DL, Potkin SG et al (1999) Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone Study Group. Neuropsychopharmacology 20:491–505CrossRefPubMedGoogle Scholar
  15. De Hert M, Detraux J, vanWinkel R et al (2011) Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol 8:114–126CrossRefPubMedGoogle Scholar
  16. Foley DL and Morley KI (2011) Systematic review of early cardiometabolic outcomes of the first treated episode of psychosis. Arch Gen Psychiatry 68:609–616Google Scholar
  17. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18(6):499–502PubMedGoogle Scholar
  18. Grootens KP, van Veelen NM, Peuskens J et al (2011) Ziprasidone vs olanzapine in recent-onset schizophrenia and schizoaffective disorder: results of an 8-week double-blind randomized controlled trial. Schizophr Bull 37(2):352–361CrossRefPubMedGoogle Scholar
  19. Hjorthøj C, Stürup AE, McGrath JJ et al (2017) Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis. Lancet Psychiatry 4(4):295–301Google Scholar
  20. Jensen KG, Correll CU, Rudå D et al (2017) Pretreatment cardiometabolic status in youth with early-onset psychosis: baseline results from the TEA trial. J Clin Psychiatry.
  21. Kahn RS, Fleischhacker WW, Boter H et al (2008) Effectiveness of antipsychotic drugsin first-episode schizophrenia and schizophreniform disorder: an openrandomised clinical trial. Lancet 371(9618):1085–1097CrossRefPubMedGoogle Scholar
  22. Kane JM, Carson WH, Saha AR et al (2002) Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry 63:763–771CrossRefPubMedGoogle Scholar
  23. Karayal ON, Glue P, Bachinsky M et al (2011) Switching from quetiapine to ziprasidone: a sixteen-week, open-label, multicenter study evaluating the effectiveness and safety of ziprasidone in outpatient subjects with schizophrenia or schizoaffective disorder. J Psychiatr Pract 17(2):100–109CrossRefPubMedGoogle Scholar
  24. Kerwin R, Millet B, Herman E et al (2007) A multicentre, randomized, naturalistic, open-label study between aripiprazole and standard of care in the management of community-treated schizophrenic patients Schizophrenia Trial of Aripiprazole: (STAR) study. Eur Psychiatry 22:433–443CrossRefPubMedGoogle Scholar
  25. Kinon BJ, Lipkovich I, Edwards SB et al (2006) A 24-week randomized study of olanzapine versus ziprasidone in the treatment of schizophrenia or schizoaffective disorder in patients with prominent depressive symptoms. J Clin Psychopharmacol 26:157–162CrossRefPubMedGoogle Scholar
  26. Komossa K, Rummel-Kluge C, Hunger H et al (2009) Ziprasidone versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 4:CD006627Google Scholar
  27. Lee SY, Park MH, Patkar AA et al (2011) A retrospective comparison of BMI changes and the potential risk factors among schizophrenic inpatients treated with aripiprazole, olanzapine, quetiapine or risperidone. Prog Neuropsychopharmacol Biol Psychiatry 35(2):490–496CrossRefPubMedGoogle Scholar
  28. Li Q, Chen D, Liu T et al (2016) Sex differences in body mass index and obesity in Chinese patients with chronic schizophrenia. J Clin Psychopharmacol 36(6):643–648CrossRefPubMedGoogle Scholar
  29. Lieberman JA, Stroup TS, McEvoy JP et al (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353:1209–1223CrossRefPubMedGoogle Scholar
  30. Lingjaerde O, Ahlfors UG, Bech P et al (1987) The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand Suppl 334:1–100CrossRefPubMedGoogle Scholar
  31. Maayan L, Correll CU (2011) Weight gain and metabolic risks associated with antipsychotic medications in children and adolescents. J Child Adolesc Psychopharmacol 21(6):517–535CrossRefPubMedGoogle Scholar
  32. Mackin P, Waton T, Watkinson HM et al (2012) A four-year naturalistic prospective study of cardiometabolic disease in antipsychotic-treated patients. Eur Psychiatry 27(1):50–5Google Scholar
  33. Malla A, Mustafa S, Rho A et al (2016) Therapeutic effectiveness and tolerability of aripiprazole as initial choice of treatment in first episode psychosis in an early intervention service: a one-year outcome study. Schizophr Res 174(1–3):120–125. CrossRefPubMedGoogle Scholar
  34. Matthews DR, Hosker JP, Rudenski AS et al (1985) Homeostasis model assessment: insulin resistance and betacell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419CrossRefPubMedGoogle Scholar
  35. McEvoy JP, Daniel DG, Carson WH Jr et al (2007) A randomized, double-blind, placebo-controlled, study of the efficacy and safety of aripiprazole 10, 15 or 20 mg/day for the treatment of patients with acute exacerbations of schizophrenia. J Psychiatr Res 41:895–905CrossRefPubMedGoogle Scholar
  36. McLaughlin T, Reaven G, Abbasi F et al (2005) Is there a simple way to identify insulinresistant individuals at increased risk of cardiovascular disease? Am J Cardiol 96(3):399–404CrossRefPubMedGoogle Scholar
  37. Pappadopulos E, Newcomer JW, Kolluri S (2012) Changes in weight, plasma lipids, and glucose in adults treated with ziprasidone: a comprehensive analysis of Pfizer-initiated clinical trials. J Clin Psychiatry 73:e742–e748CrossRefPubMedGoogle Scholar
  38. Parabiaghi A, Tettamanti M, D’Avanzo B et al (2016) Metabolic syndrome and drug discontinuation in schizophrenia: a randomized trial comparing aripiprazole olanzapine and haloperidol. Acta Psychiatr Scand 133(1):63–75CrossRefPubMedGoogle Scholar
  39. Pelayo-Terán JM, Pérez-Iglesias R, Ramírez-Bonilla M et al (2008) Epidemiological factors associated with treated incidence of first-episode non-affective psychosis in Cantabria: insights from the Clinical Programme on Early Phases of Psychosis. Early Interv Psychiatry 2(3):178–187CrossRefPubMedGoogle Scholar
  40. Perez-Iglesias R, Crespo-Facorro B, Amado JA et al (2007) A 12-week randomized clinical trial to evaluate metabolic changes in drug-naive, first-episode psychosis patients treated with haloperidol, olanzapine, or risperidone. J Clin Psychiatry 68(11):1733–1740CrossRefPubMedGoogle Scholar
  41. Perez-Iglesias R, Crespo-Facorro B, Martinez-Garcia O et al (2008) Weight gain induced by haloperidol, risperidone and olanzapine after 1 year: findings of a randomized clinical trial in a drug-naïve population. Schizophr Res 99(1–3):13–22CrossRefPubMedGoogle Scholar
  42. Perez-Iglesias R, Mata I, Pelayo-Teran JM et al (2009) Glucose and lipid disturbances after 1 year of antipsychotic treatment in a drug-naïve population. Schizophr Res 107(2–3):115–121CrossRefPubMedGoogle Scholar
  43. Pérez-Iglesias R, Ortiz-Garcia de la Foz V, Martínez García O et al (2014a) Comparison of metabolic effects of aripiprazole, quetiapine and ziprasidone after 12 weeks of treatment in first treated episode of psychosis. Schizophr Res 159(1):90–94CrossRefPubMedGoogle Scholar
  44. Pérez-Iglesias R, Martínez-García O, Pardo-Garcia G et al (2014b) Course of weight gain and metabolic abnormalities in first treated episode of psychosis: the first year is a critical period for development of cardiovascular risk factors. Int J Neuropsychopharmacol 17(1):41–51CrossRefPubMedGoogle Scholar
  45. Pillinger T, Beck K, Gobjila C et al (2017) Impaired glucose homeostasis in first-episode schizophrenia: a systematic review and meta-analysis. JAMA Psychiatry 74(3):261–269CrossRefPubMedGoogle Scholar
  46. Rummel-Kluge C, Komossa K, Schwarz S et al (2010) Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res 123:225–233CrossRefPubMedPubMedCentralGoogle Scholar
  47. Spurling RD, Lamberti JS, Olsen D et al (2007) Changes in metabolic parameters with switching to aripiprazole from another second-generation antipsychotic: a retrospective chart review. J Clin Psychiatry 68:406–409CrossRefPubMedGoogle Scholar
  48. Stahl SM, Mignon L, Meyer JM (2009) Which comes first: atypical antipsychotic treatment or cardiometabolic risk? Acta Psychiatr Scand 119(3):171–9Google Scholar
  49. Stroup TS, Lieberman JA, McEvoy JP et al (2006) Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am J Psychiatr 163:611–622CrossRefPubMedGoogle Scholar
  50. Stroup TS, McEvoy JP, Ring KD et al (2011) A randomized trial examining the effectiveness of switching from olanzapine, quetiapine, or risperidone to aripiprazole to reduce metabolic risk: comparison of antipsychotics for metabolic problems (CAMP). Am J Psychiatry 168:947–956CrossRefPubMedPubMedCentralGoogle Scholar
  51. Takeuchi H, Uchida H, Suzuki T et al (2010) Changes in metabolic parameters following a switch to aripiprazole in Japanese patients with schizophrenia: one-year follow-up study. Psychiatry. Clin Neurosci 64:104–106CrossRefGoogle Scholar
  52. Zhai D, Lang Y, Feng Y et al (2017) Early onset of cardiometabolic risk factor profiles in drug naïve adolescents and young adults with first-episode schizophrenia. Schizophr Res pii: S0920-9964(17):30126–30123Google Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Javier Vázquez-Bourgon
    • 1
    • 2
    • 3
    Email author
  • Rocío Pérez-Iglesias
    • 2
    • 4
  • Víctor Ortiz-García de la Foz
    • 1
    • 2
  • Paula Suárez Pinilla
    • 1
    • 2
    • 3
  • Álvaro Díaz Martínez
    • 2
    • 3
    • 5
  • Benedicto Crespo-Facorro
    • 1
    • 2
    • 3
  1. 1.Department of PsychiatryUniversity Hospital Marqués de Valdecilla-IDIVALSantanderSpain
  2. 2.CIBERSAM: Centro de Investigación Biomédica en Red en Salud MentalMadridSpain
  3. 3.School of MedicineUniversity of CantabriaSantanderSpain
  4. 4.Psychosis Studies DepartmentInstitute of Psychiatry, Psychology and NeuroscienceLondonUK
  5. 5.IBBTEC: Instituto de Biomedicina y Biotecnología de CantabriaSantanderSpain

Personalised recommendations